Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3.
Article Details
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Engler TA, Henry JR, Malhotra S, Cunningham B, Furness K, Brozinick J, Burkholder TP, Clay MP, Clayton J, Diefenbacher C, Hawkins E, Iversen PW, Li Y, Lindstrom TD, Marquart AL, McLean J, Mendel D, Misener E, Briere D, O'Toole JC, Porter WJ, Queener S, Reel JK, Owens RA, Brier RA, Eessalu TE, Wagner JR, Campbell RM, Vaughn R
Substituted 3-imidazo[1,2-a]pyridin-3-yl- 4-(1,2,3,4-tetrahydro-[1,4]diazepino-[6,7,1-hi]indol-7-yl)pyrrole-2,5-diones as highly selective and potent inhibitors of glycogen synthase kinase-3.
J Med Chem. 2004 Jul 29;47(16):3934-7.
- PubMed ID
- 15267232 [ View in PubMed]
- Abstract
Glycogen synthase kinase-3 (GSK3) is involved in signaling from the insulin receptor. Inhibitors of GSK3 are expected to effect lowering of plasma glucose similar to insulin, making GSK3 an attractive target for the treatment of type 2 diabetes. Herein we report the discovery of a series of potent and selective GSK3 inhibitors. Compounds 7-12 show oral activity in an in vivo model of type II diabetes, and 9 and 12 have desirable PK properties.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Staurosporine Glycogen synthase kinase-3 beta IC 50 (nM) 56 N/A N/A Details